216. Baseline soluble immune checkpoints predict relapse risk in PR3-ANCA vasculitis following rituximab induction therapy

Background: We investigated whether soluble immune checkpoints (sICPs) predict treatment-resistance, relapse risk, and risk of infections in patients with anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV).

Methods: Plasma levels of sICPs were measured by enzyme-linked immunosorbent assay from samples obtained at baseline and during follow-up from patients with AAV in the RAVE trial and were correlated with selected clinical outcomes. Log rank test was used to evaluate survival benefits. Optimal cut-off values of the marker molecules were calculated using Yeldons J.

Results: Among 95 patients receiving rituximab as induction therapy, lower soluble (s)Lag-3 (< 90 pg/mL) and higher sCD27 (> 3000 pg/mL) were predictive of not achieving remission. Among patients with remission, 32.9% relapsed with a median relapse free survival of 5.64 months. Low baseline values of sTim-3 (< 1200 pg/mL), sCD27 (< 1250 pg/mL), and sBTLA (< 1000 pg/mL) were associated with disease relapse (see Figure 1). In addition, patients with high levels of at least one of these marker were prone to infectious complications. These findings were restricted to patients with proteinase 3 (PR3)-ANCA vasculitis and not observed in patients with myeloperoxidase (MPO)-ANCA vasculitis. Moreover, these relationships do not hold for the group of patients randomised to receive cyclophosphamide/azathioprine.

Conclusions: Rituximab-treated patients achieved remission less frequently when sLag-3 was low and sCD27 was high. Higher expression of sTim-3, sCD27, and sBTLA at baseline was associated with a lower risk of relapse in PR3-ANCA vasculitis following rituximab. These results will require confirmation in future studies, but may contribute to personalized medicine in AAV.

Disclosures: AK received Consultancy Fees from Otsuka, Alexion, Vifor Pharma, UriSalt and Catalyst Biosciences.

Figure 1. Kaplan-Meier curves for the duration of complete remission in rituximab treated patients in months from the time point of complete remission achievement. Relapse defined the event. The combination of those three markers using the predefined cut offs in RTX treated patients.